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1 Mutations Mutations: 2 general ways to alter DNA Change a single DNA base Or entire sections of DNA can move from one place to another What is a mutation? Any change in the nucleotide sequence of DNA Here a single base is changed: Changes in a single DNA base Caused by errors in DNA replication, UV radiation, or chemical carcinogens Misspelling Mutations are rare

2 Mistakes happen DNA repair DNA proofreading mechanisms correct these mistakes The daughter strand is compared to the parent DNA to check for mistakes Proofreading is not perfect mutations are still possible, although rare Mutations key features Mutations are rare changes in DNA But they can affect genes and the proteins they encode Mutations are inherited only if they occur in germ-line cells Mutations are important for genetic variation and evolutionary change Mutations & human evolution: Digesting the sugar in milk Lactose is digested by the enzyme lactase. In most human populations the activity of this enzyme is dramatically reduced after weaning. A simple mutation created lactose tolerance In some populations, the lactase enzyme is present in adults Mutation is found primarily in dairying populations Appears to be an evolutionary adaptation to eating dairy products Genetic trait has only evolved recently Genetic basis of lactose tolerance A mutation in the regulatory DNA (promoter) that controls transcription of the gene The lactase gene continues to be transcribed in adults Allows some groups to digest milk C T Lactase gene The biology of cancer Mutations can cause cancer

3 Cancer the leading cause of death in U.S. Characteristics of cancer cells Nearly one-third of us will develop cancer in our lifetimes Cancer is not a single disease Abnormal shape Not specialized Immortal (able to divide continually) Incidence of cancer Normal cervical cells Cervical cancer cells What Is Cancer? Cancer has many causes Uncontrolled cell division Caused by break-down in the normal mechanisms of cell regulation Normal cells are programmed to die if their DNA is damaged Mutations that damage DNA Environmental carcinogens Some viruses Apoptosis Tobacco smoke X-rays UV radiation in sunlight and tanning lamps HPV virus Hepatitis B and C viruses Epstein-Barr virus Heredity Diet 3D Medical Animation - What is Cancer? 1:06 Mutations in tumor suppressor proteins cancer Changes in DNA can cause normal cells to become cancerous Oncogene Turned On Cancers can be caused by DNA mutations that turn on oncogenes (genes that speed up cell division) Tumor Suppressor Gene Turned Off Or by mutations that turn off genes that slow down cell division or cause cells to die at the right time In healthy cells, tumor suppressor proteins keep cell division in check by killing damaged cells

4 Mutations in proto-oncogenes cancer Proto-oncogenes are growth factors that speed up cell division When they are mutated, they form oncogenes, or genes that cause uncontrolled cell growth Mutations in DNA repair genes cause cancer DNA repair or proofreading genes make enzymes that help the cell fix mutations in its DNA. When a DNA repair gene is mutated, the cell can t repair mistakes in its DNA. These mistakes build up until a proto-oncogene is hit. Then the cell becomes cancerous. Mutations in different genes cause cancer The Progression of a Cancer Growth factors Tumor-suppressor genes DNA repair proteins Proteins that regulate cell division Cancer develops after a series of mutations Cancer develops after a series of mutations Why cancer cells form tumors The Immune System fights Cancer Normal cells stop dividing when they come in contact with a neighbor Cancer cells have lost all restraint Pile on top of one another Grow in multiple layers T cell attacking 2 large tumor cells The immune system destroys most potentially cancerous cells it recognizes cancer cells as different or nonself Usually, killer T cells and NK cells recognize abnormal proteins on the surface of tumor cells and destroy them

5 What is a benign tumor? A malignant tumor? Is Cancer Inherited? Usually not Most mutations occur in the organ where the cancer starts e.g. the colon or lung Normally germ-line cells aren t affected the mutations are not passed from parent to child But cancer-causing mutations sometimes do occur in gametes What causes breast cancer? Many risk factors Hormones Gene mutations Radiation Cancer-causing chemicals Most breast cancers are not caused by inherited mutations BRCA1 and BRCA2, inherited cancer genes In healthy cells, BRCA1 and BRCA2 genes are tumor suppressors. BRCA1 and BRCA2 help prevent uncontrolled cell growth. When they are mutated, they no longer suppress abnormal growth, and cancer is more likely to develop. Mutations and breast cancer Your friend tells you she recently had genetic testing done, and her doctor said she inherited a single mutation in a gene that is connected to breast cancer. Your friend is unsure what this means and is worried she will definitely get breast cancer later in life. What is your understanding of what the doctor said? Is this person certain to get cancer later? SU2C: the BRCA gene (1:51) Environment and Cancer Tobacco smoke Industrial pollutants Lung and other cancers are caused by environmental carcinogens

6 Environment and Cancer Viruses and Cancer Viruses can also promote cancerous mutations Viruses linked to particular cancers: UV light can penetrate cells and damage DNA Vaccine for HPV Over 80% of skin cancers are caused by exposure to UVB radiation from the sun Diet and Cancer Diet and Cancer Obesity linked to Certain foods may help guard against cancer Foods rich in antioxidants increase in colon cancer among both men and women increase in breast and uterine cancer among women (carotenes, vitamins C and E) Diets high in animal fat (beef, pork, and dairy foods) linked with increased risk of colon cancer Excessive alcohol consumption linked to increases in many forms of cancer Antioxidants counteract the effects of the free radicals that are a normal byproduct of cell metabolism cancers of the mouth, throat, and esophagus breast and liver cancers Cancer Treatment surgery radiation therapy chemotherapy free radicals are generally detoxified by the body but if they build up in the body, they can damage other molecules, including DNA Cancer Treatment Focused on killing or removing the primary tumor and then attacking any metastastic tumors that may be present Standard treatments Human papilloma virus (HPV) cervical cancer Epstein Barr virus (EBV) Hodgkin s and non-hodgkin s lymphoma Hepatitis B and C viruses liver cancer Chemotherapy Radiation therapy Radiation therapy Drugs used to attack cancers that have spread Kills fast-growing (dividing) cells Stops cell growth only where the radiation beam is aimed Neither distinguish between cancer cells and healthy cells

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